Laboratory tests during resuscitation

The Journal

ofEmergency Medicine, Vol.

7, pp. 451-456,

LABORATORY

Copyright 0 1989 Pergamon Press plc

??

TESTS DURING RESUSCITATION

Raymond M. Fish, ‘Burnham

Printed in the USA

1989

PhD, MD, FACEP*

Hospital, Champaign,

and Lenora Louie, Bst

Illinois and *University

of Illinois, Urbana, Illinois

Reprintaddress: Dr. Raymond M. Fish, 801 McHenry Street, Urbana, IL 61801

0 Abstract-The drawing of laboratory tests is often overlooked in the moribund patient. In patients with medical problems, potassium and other electrolyte abnormalities are often of significance and may be the cause of the arrest. Patients without circulation begin to develop severe abnormalities of PT, PTT, and potassium. These measurements will sometimes demonstrate that a patient’s condition is hopeless. When laboratory tests show a situation to be hopeless, an early cessation of resuscitation efforts will be possible, and the justification for such actions will be documented. Laboratory tests drawn early in the resuscitation effort may prove that resuscitation could not have been successful.

should be stopped. In most cases resuscitation is (and should be) stopped on clinical grounds before such laboratory abnormalities develop. Therefore, these tests are not meant to be a substitute for (or verification of) clinical judgment. In a small percentage of resuscitations, however, laboratory tests will prove useful when deciding to stop resuscitation.

MATERIALS AND METHODS

Records of patients who had unsuccessful resuscitation attempts over a two-year period (January 1987 through January 1989) were reviewed. All patients were emergency department patients except for patient 5 who had previously been admitted for sepsis. Cases were selected on the basis of laboratory test result availability. No tests were taken after a patient was pronounced dead (i.e., after resuscitation efforts were stopped) except for toxicology studies requested by the coroner. Patients were not included in the study if they survived the resuscitation or if blood samples were reported to be hemolyzed.

0 Keywords-death; resuscitation; laboratory; electrolytes; forensic

INTRODUCTION

Blood tests drawn during a resuscitation can give information that is valuable for guiding treatment. In the patient with cardiac dysrhythmias, electrolyte levels and blood gases are especially useful. There is sometimes no immediately clear diagnosis when a patient presents in severe distress or with actual respiratory or cardiac arrest. Laboratory tests can sometimes help to establish a diagnosis and guide treatment. Blood can often be obtained while a physician or nurse is starting an IV, or the blood can be drawn by a laboratory technician so as not to slow the resuscitation process. Patients without circulation slowly develop severe abnormalities of PT, PTT, and potassium. Therefore, laboratory tests will sometimes document the fact that a patient’s condition is hopeless and resuscitation

w

RESULTS

Our data show post arrest laboratory changes that are consistent with the past literature on this subject (as described in the discussion section). Elevations of serum potassium, PT, and PTT occurred in patients who were thought to have been without circulation for significant periods of time. The four patients who had unwitnessed arrests (patients 2, 8, 14, and 15) had potassium levels of

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452

Raymond M. Fish, Lenora Louie

11.5, 6.5, 12.2, and 7.5. Times were approximate in some cases, and potassium is influenced by several factors discussed below. Nevertheless, potassium clearly rises with time, as shown in Figure 1. All of the PT and PTT values measured for the patients with unwitnessed arrests were significantly elevated. Other laboratory tests did not show as definite a relationship between time after cardiac arrest and changes in lab values. Results obtained are shown in Tables l-6 along with other patient information and discussed in the Discussion section. ?? (3

2

DISCUSSION

0

I 20

I 40

Minutes

I 60

‘L

80

(t)

Potassium Jetter (1) found that potassium levels rise to 18 mEq/L in the first hour after death, followed by gradual increases to 25 mEq/L at 12 to 24 hours. Hemolysis of blood, caused by drawing blood with too much force through a small needle, will artificially raise serum potassium level measurements (2). Changes in ventilation and the administration of sodium bicarbonate or glucose during CPR will affect the potassium level. Administration of epinephrine will also lower serum potassium, due to beta, stimulation (3). Hypokalemia may be responsible for many cardiac arrests, but this is unproven and controversial (4,5). Factors that change potassium levels during CPR make calculation of pre-arrest potassium levels difficult, if not impossible (3,6,7). Thus, potassium levels measured during or shortly after a resuscitation attempt will not accurately tell one what the pre-arrest potassium level was, though the levels can be useful in directing patient treatment. Extremely high potassium levels may be due to preexisting hyperkalemia, but in most cases will be due to the postmortem changes described by Jetter (1). For example, in our study the highest potassium level was in a 16-year-old male who had a 45-minute extrication time following an automobile accident. He was thought to have been in cardiac arrest during that entire time. The potassium level of 12.2 suggests that the patient was in cardiac arrest during the extrication. Patients thought to have been without circulation for prolonged periods of time are sometimes successfully resuscitated. Hypotension and shallow breathing can be interpreted as cardiac and respiratory arrest by paramedics as well as lay persons, making attempts at resuscitation in seemingly hopeless cases

Figure 1. Time between arrest and drawing of blood. All times are approximate. Patient 5 is not shown. A polynomial approximation to the data is Kz4.0 -O.OWt+ .OOOlW + .000019P

occasionally rewarding. The finding of a potassium level that is incompatible with life, however, verifies the hopelessness of the situation. The other extremely high (11.5) potassium level was in patient number 2, who was found lifeless in a detox center. The time of arrest was unknown, but the potassium level suggests the time was long and the situation was hopeless. The one low potassium level (2.6) was in a patient with a history of hypertension who spontaneously arrested at home. Diuretic-induced hypokalemia would be a plausible explanation in this case.

Sodium Jetter (1) found that plasma Na concentration remained constant until at least 12 hours after death. On the other hand, Coe (8,9) found Na levels held constant for only approximately the first few hours after death and then gradually declined, with great individual variation. Other investigators have approximately the average rate of fall to be 0.9 mEq/L per hour. With two exceptions, all of our patients had normal serum sodium levels. Patient 5 had been in septic shock with preexisting electrolyte imbalance long before arresting. Patient 13 had an unexpected cardiac arrest while taking a walk, and his elevated sodium level of 162 is unexplained.

Laboratory

453

Tests During Resuscitation

Table 1. Patient Histories Age, years

Patient

Sex

History

M M M M M F M F M

3 hours of chest pain before arrest at home Found dead at detox center. Aspiration. Cardiac arrest during exertion. Aspiration. Passed out at work. Woke with good blood pressure. Then arrested in ambulance. Group A beta strep necrotizing fasciitis. Creatinine was 3.4 half a day (11.5 hours) before arrest. Found with slow ventricular rhythm at home. Neck and chest gunshot wounds. Cocaine found on toxicology test. Hanging by the neck for possibly as long as 45 minutes. Increasing shortness of breath over 4 days. Cardiac arrest at home. Cardiac arrest at home. Cardiac arrest at home. Cardiac arrest taking a walk. Auto accident with arrest before paramedics arrived. Forty-five minute extrication time. Found dead 1 week after surgery. Pulmonary emboli.

71 60 56 49 33 91 37 75 73 57 73 57 61 16 29

1

2 3 4 5 6 7 8 9 10 11 12 13 14 15

M M M

M M M

Table 2. Patient Data’ Patient 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

PT

BUN

Na

K

Cl

Glut

13 21 12 14.5 >lOO 13 20 49 15 13 13.5

22 9 15 13 39 14 6 15 46 11 15 13 11 11 17

141 141 139 144 129 144 141 141 145 133 139 141 162 147 145

2.6 11.5 4.8 3.9 6.4 5.0 4.8 6.5 7.8 5.9 3.8 3.2 6.3 12.2 7.5

104 100 106 115 97 106 113 108 101 107 102 103 99 100 101

276 181 82 157 174 115 27 237 153 220 418 198 426 198 288

PTT

> 200

> 200 38 > 200 30

> 200 70

Blood Urea Nitrogen

> 200 17.5

‘Times are not accurately

known, especially for unwitnessed

arrests.

LDH

SGOT

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

155 1474 142 141 637 260 217 200 679 276 165 214

4800

mg/dL .

Our two patients with significant elevation of BUN had been ill for several days and probably had elevation of BUN before their arrest. Patient 5 had necrotizing fasciitis, and patient 9 had had increasing shortness of breath over 4 days. Glucose

Table 3. Patient Data

Patient

Coe’s study of 100 cases found little change in BUN within 24 hours of death (9). Changes in BUN when measured pre- and post-mortem averaged 13.8 mg/dL in patients with normal renal function and about 3 mg/dL in patients with initial nitrogen retention. Fekete and Kerenyi (10) also supported these results, concluding that healthy persons who died suddenly had similar BUN levels in premortem and postmortem periods-within the normal range of 5 to 25

AlkP

Chol

22 402 17 51 230 14 91 37 173 63 20 46

53 89 75 41 33 40 25 67 29 88 54

155 167 268 93 28 211 52 243 170 212 146

1810

78

172

Without CPRt

With CPRS

5 54’ 6 0 0 5 0 27*

40 6 30 7 16 36 23 18 60 24 47 16 60’ 25 60

15

45’ 10’

twithout CPR = time without CPR before tests were drawn, minutes. *With CPR = time with CPR before tests were drawn. *Times are not accurately known, especially for unwitnessed arrests.

All of our patients had normal or elevated glucose levels except patient number 7. Patient 7 had severe blood loss with just glucose-free crystalloid replacement at the time blood tests were drawn. Just before death, blood sugar often rises due to stress. Peripheral hyperglycemia above 650 mg/dL is unlikely to be found in nondiabetics. Glycolysis can occur in postmortem peripheral venous blood, while blood taken from the right atrium may have higher glucose values from glycogenolysis in the liver (7). Glycogen will persist in the liver after death and will only gradually fall off with time. Due to glycogenolysis in the liver, blood glucose is found to be higher in samples taken from the right atrium than in those taken from the left (11). Jetter (1) supports the fact that there is variation between blood glucose lev-

454

Raymond M. Fish, Lenora Louie Table 4. Patient Data Patient

T Bili

Creat

T Pro

Album

Ca

Phos

UricA

:

0.35 0.27

1.4 .6

5.6

3.1 3.4

6.6

11 5.2 5

2.9 7.6

3 4 5 6 7

0.31 0.13 0.66 0.46

1.3 1.0 5.1 1.2

7.2 3.2 3.3 6.9

4.0 1.7 2.0 3.5

t’: 414 6.0 9.2

9’6 416 2.0 10.9

:::

0.11 0.25 0.76 0.31 0.47

0.7 1.4 1.6 1.3 1.4

2.5 6.9 5.9 6.5 5.7

1.3 3.7 i:: 3.1

6.6 9.6 9.2 66 10:6

4.2 6.7 15.3 79 9:3

0.67

2.3

7.0

3.9

9.9

6 9 10 11 12 15

Table 5. Blood Gases’ Patient 2. 4. 5. 6. 9. 10. 10. repeat 12. 13. 15.

PH 6.465 7.271 7.322 7.057 6.982 6.986 7.208 7.220 6.736 8.749

pco2 207.8 44.8 23.4 12.6 90.4 86.6 33.5 30.8 143.8 98.2

HC03 5.1 5.1 40.7 432.6 2.9 16.4 136.5 82.9 14.8 7.9

Bicarb’

15.6 20.5 12.1 3.5 21.4 20.6 13.3 12.6 13.3

Table 6. Normal Laboratory Values In our Laboratory at the Time of the Study

Total bilirubin Creatinine Total protein Albumin Calcium Phosphorus Uric acid CPK LDH SGOT/AST Alkaline phos Cholesterol P-I-T PT BUN Na

Units

:I Glut PH PC02 PC2 HCOs

0.12-1.25 0.9-1.3 6.4-7.9 4.1-5.1 8.4-10.2 2.3-4.0 4.2-8.6 33-213 92-186 7-32 29-92 132-299 21-42 10.5-14.5 5-25 135-153 3.5-5.3 97-110 60-110 7.38-7.46 32-46 74-108 21-29

Ei 6:l 5.; 717 5.6

145 97 60 51 4520 76 669 37 200 193 62 260 240

els taken from the left and right side of the heart. Hence, it is difficult to establish a postmortem “normal.” Other studies have reported that CSF glucose levels are better indicators of postmortem glucose because there are so many factors influencing blood glucose levels (Table 7). Fekete and Kerenyi provide a table summarizing these factors (10).

PTand PTT

19.3

*Ampules of sodium bicarbonate given before drawing gases. Blood gas determinations may have been performed on venous blood in some cases due to lack of pulses. Gases were repeated after reintubation on patient 10.

Laboratory Test

7.7

CPK

mgldL mgldL gldL g/dL mg/dL mg/dL mg/dL IUlL IUlL IUlL IUlL mgldL seconds seconds mgldL mEq/L mEq/L mEq/L mEq/L mmHg mmHg mmoL/L

Trauma, oligemic shock, sepsis, and many other conditions are known to induce consumption coagulopathy (12). Stasis of blood, as in the pericardium or peritoneal cavity, will deplete blood of its clotting factors. PT and PTT did remain normal in two of our patients who had CPR for over 40 minutes. The other patients who did develop elevations of PT and PTT had 1) longperiods without CPR (stasis), 2) sepsis, or 3) trauma. PTT was elevated above 200 seconds in the two patients (2 and 14) who had high potassium levels and who were thought to have had prolonged cardiac arrest with late initiation of CPR. Patient 5 had extreme elevations of PT and PTT, probably due to consumption coagulopathy associated with a necrotizing fasciitis and group A beta-hemolytic strep sepsis. Patient 8 was found hanging by the neck and had been that way for 45 minutes or less- the PT was 49 seconds. Patient 7 had been shot and had a cardiac arrest about 23 minutes before blood was drawn. There was a slight elevation of PT and a very high PTT, possibly due to extensive bleeding and replacement with crystalloid only at the time blood was drawn (dilution of clotting factors by replacement fluids). Patient 15 had CPR for an hour after being found lifeless. He had had surgery a week earlier and large pulmonary emboli were found at autopsy. limo patients (numbers 6 and 9) had CPR for 41 or more minutes before blood tests were drawn, yet the PT and PTT were normal.

Laboratory

TestS During Resuscitation

Table 7. Factors

Affecting

Postmortem

455

Blood Sugar Levels

A. Factors tending to raise postmortem blood sugar 1. liver glycogenolysis 2. bacterial breakdown of carbohydrates in the gastrointestinal tract and in the tissues 6. Factors tending to lower postmortem blood sugar 1. oxidative glycolysis by cells still living 2. anaerobic glycolysis by dying cells and free enzymes 3. anaerobic glycolysis by bacteria C. Factors influencing A & B 1. time elapsed since clinical death 2. temperature of body 3. amount of liver glycogen available (liver disease, nutritional state) 4. amount of food present in the gastrointestinal tract at the time of death

Alkaline Phosphatase Coe (8) found an average increase of about 20% in alkaline phosphatase levels in the 2 hours following death. Data recorded by Naumann (13) also supports Coe’s conclusions. Lythgoe (14) went a step further and measured postmortem alkaline phosphatase from different sites of the body, namely, from the arms, legs, and both sides of the heart. He showed that alkaline phosphatase activity increased with time after death. All of our patients had normal alkaline phosphatase values. Bilirubin Naumann (13), based on 12 cases, found that postmortem values were similar to antemortem values. However, Coe (7,8) found a slight rise in total bilirubin, averaging about 20% higher in the 2 hours following death. All of our total bilirubin measurements were within normal limits (0.12-1.25 mg/dL) except for patient 7 whose 0.11 mg/dL result may have been the result of dilution by replacement fluid. Lactic Acid Jetter (1) found that lactic acid increases from a normal of about 1 mEq/L in life to about 20 mEq/L at one hour after death. Jetter reported that during the 12 to 24 hours postmortem, lactic acid values reached levels 50 to 75 times higher than antemortem levels. Though we did not measure lactic acid, it probably did contribute to the acidosis seen in our patients. Creatinine, Cholesterol, Cortisol, Calcium, and Protein Creatinine, cholesterol, cortisol, and protein change little in postmortem blood (7). Naumann’s (15) stud-

ies with creatinine, cholesterol, and protein were all in agreement with Coe’s results. Several of our patients had slightly elevated creatinine levels, which may have been present before death. The one (septic) patient with a very high creatinine level (number 5) had an elevated creatinine (3.4) measured 11.5 hours before he arrested. Total protein and albumin were measured as being abnormally low in almost all of our patients, a result that does not agree with expectations. The lowest value (patient 7) occurred in the patient with significant vascular dilution, but the results from the rest of the patients are not adequately explained. Calcium levels were correspondingly low, presumably because of calcium binding to albumin.

Blood Gases In one study, aortic oxygen tension (PO,) in patients who died of cardiac arrest while on respirators ranged from 35 to 82; the blood samples were taken 1.5 or more hours after death (7). Patients who died of respiratory arrest (respirator turned off while the heart was still beating) had p0, levels between 3 and 12. Plasma pH averaged 6.73 hours for the first 12 hours after death and 6.43 for the next 12 hours in another study (1). It is interesting to note that oxygen remains in the blood for more than an hour after circulation stops. However, our results cannot be directly compared to the above postmortem measurements because our tests were drawn during CPR, while circulation and respiration were (presumably) being continued. During CPR blood gas changes occur continuously, reflecting the effectiveness of the therapy and the response of the patient. In all of our patients placement of the endotracheal tube was verified by listening over the abdomen and lung fields. In many cases tube placement was also verified by direct visualization. In patient 10 the tube placement (by paramedics) was found to be improper. The first gases were drawn as the patient was being re-intubated. The second set was drawn 5 minutes later. Even though this patient had suffered prolonged hypoxia with totally ineffective oxygenation during CPR, normalization of his p0, and pC0, was possible with reintubation. Patient 2 was noted to have aspirated, and blood gases could not be corrected. The blood gases of several additional patients could not be corrected. The blood gases of patient 4 might well have been taken on venous blood, as it is difficult to distinguish arterial and venous pulsations during CPR. The blood gases of patients 9, 15, and possibly of patient 13 suggest inadequate ventilation

456

Raymond M. Fish, Lenora Louie

or perfusion. If these patients had arrested because of pulmonary embolus, inadequate vascular volume, or a variety of other causes, the situation could be explained. Autopsy information was available for patient 15 alone, and it did show massive pulmonary emboli. SUMMARY The drawing of laboratory tests is sometimes overlooked in the moribund patient. In the myocardial infarction patient, measurement and normalization of electrolytes and blood gases may improve cardiac responsiveness to resuscitative measures (ACLS protocols). Our data suggest that patients without circulation develop severe abnormalities of PT, PTT, and potassium. Jetter (1) found that potassium levels rise to 18 mEq/L in the first hour after death. Of our 15 patients, 7 had potassium levels of 6.0 mEq/L or great-

er, and 2 patients had potassium levels of 11.5 mEq/L or greater. Though we could find no literature discussing blood coagulation after death, it is a common observation that a clot will form in blood allowed to sit in a container or body cavity, leaving free nonclotting blood. Four of the 6 patients in our study who had PTT drawn had values of greater than 200 seconds. Of the 11 patients tested, 5 had abnormally high PT measurements. Only one of these patients was known to have a preexisting condition that might be expected to give abnormal coagulation studies (patient 5 had sepsis). Normal laboratory values do not predict that it will be possible to resuscitate a patient. In most cases resuscitation should be stopped on clinical grounds before abnormalities of potassium, PT, or PTT develop. One should not wait for laboratory tests to make a clinical judgment. In a small percentage of resuscitations, however, laboratory tests will prove useful when deciding to stop resuscitation.

REFERENCES 1. Jetter WW. Post-mortem biochemical changes. J Forensic Sci. 1959;4:330-41. 2. Evans WED. Postmortem non-enzymal chemical changes. In: Kugelmass IN, ed. The chemistry of death. Springfield: Charles C Thomas; 1963:23-24. 3. Brown MJ, Brown DC, Murphy MB. Hypokalemia from Betaz-receptor stimulation by circulating epinephrine. N Engl J Med. 1983;309:1414-19. 4. Thompson RG, Cobb LA. Hypokalemia after resuscitation from out-of hospital ventricular fibrillation. JAMA. 1982;248: 2860-3. 5. Ruder MA, Flaker CC, Alpert MA, Bertuso J. Hypokalemia as a cause of cardiac arrest: results of electrophysiologic testing and long term follow-up. Am Heart J. 1985;110:490-1. 6. Isner JM, Harten JT. Factitious lowering of the serum potassium level after cardiopulmonary resuscitation. Arch Intern Med. 1985;145:161-2. 7. Feldman R, White RD. Hypokalemia and out-of-hospital cardiac arrest. J Emergency Medical Services. 1988;56-58. 8. Coe JI. Postmortem chemistry of blood, cerebrospinal fluid and vitreous humor. In: Fisher RS, Petty CS, eds. Forensic

pathology. National Institute of Law Enforcement and Criminal Justice, Law Enforcement Assistance Administration, US Department of Justice, July 1977, pp. 21-49. 9. Coe JI. Postmortem chemistries on blood with particular reference to urea nitrogen, electrolytes, and bilirubin. J Forensic Sci. 1974;19:33-42. 10. Fekete JF, Kerenyi NA. Postmortem blood sugar and blood urea nitrogen determinations. Can Med Assoc J. 1965;92:9703. 11. Evans WED. Postmortem non-enzymal chemical changes. In: Kugelmass IN, ed. The chemistry of death. Springfield: Charles C Thomas; 1963:27-28. 12. Carr ME. Disseminated intravascular coagulation: pathogenesis, diagnosis and therapy. J Emerg Med. 1987;5:31 l-22. 13. Naumann HN. Postmortem liver function tests. Am J Clin Pathol. 1956;26:495-505. 14. Lythgoe AS. Postmortem activity of alkaline phosphatase in serum from different sites of the cadaver cardiovascular system. J Forensic Sci Sot. 1984;337:340. 15. Naumann HN. Studies on postmortem chemistry. Am J Clin Pathol. 1950;20:314-24.